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Durvalumab (PD-L1 monoclonal antibody) + Tremelimumab (monoclonal antibody directed against CTLA-4)

Durvalumab +Tremelimumab

Paclitaxel + carboplatin

Gemcitabine + cisplatin

Gemcitabine + carboplatin

Pemetrexed + cisplatin

Pemetrexed + carboplatin

Gilberto de Castro

This is a randomized, open-label, multi-center, global, Phase III study to determine the efficacy and safety of durvalumab + tremelimumab combination therapy versus platinum-based SoC chemotherapy in the first-line treatment of patients with epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) wild-type advanced or metastatic NSCLC.

Patients will be randomized in a 1:1 to receive treatment with durvalumab + tremelimumab combination therapy or SoC therapy. The primary objective of this study is to assess the efficacy of combination treatment compared with SoC in terms of Overall Survival (OS) in patients.

Study of Durvalumab With Tremelimumab Versus SoC as 1st Line Therapy in Metastatic Non Small-Cell Lung Cancer (NSCLC) (NEPTUNE)

A Phase III Randomized, Open-Label, Multi-Center, Global Study of MEDI4736 in Combination With Tremelimumab Therapy Versus Standard of Care Platinum-Based Chemotherapy in First-Line Treatment of Patients With Advanced or Metastatic Non Small-Cell Lung Cancer (NSCLC).

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

The OS was defined as the time from the date of randomization until death due to any cause (ie, date of death or censoring - date of randomization + 1). Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. Median OS was calculated using the Kaplan-Meier technique.

OS was defined as time from date of randomization until death due to any cause (ie, date of death or censoring - date of randomization + 1). Any participant not known to have died at time of analysis was censored based on last recorded date on which participant was known to be alive.

bTMB ≥16 mut/Mb, bTMB ≥12 mut/Mb and bTMB \<20 mut/Mb analysis sets included the subset of participants in FAS whose bTMB status was ≥16 mut/Mb, ≥12 mut/Mb and \<20 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay.

PD-L1-negative analysis set included the subset of participants in FAS whose PD-L1 status was PD-L1-negative at baseline as defined by the Ventana SP263 PD-L1 Assay (ie, \<1% PD-L1-membrane expression in tumoral tissue).

bTMB non-evaluable analysis set included the subset of participants in FAS whose bTMB status at baseline could not be determined by the GuardantOMNI CDx assay or whose sample was not available.

tTMB analysis sets are defined same as the bTMB analysis sets.

The OS was defined as time from date of randomization until death due to any cause (ie, date of death or censoring - date of randomization + 1). Any participant not known to have died at the time of analysis was censored based on last recorded date on which participant was known to be alive.

Global Cohort: The FAS included all randomized participants prior to the end of global recruitment. Any participants recruited in China, after global recruitment had ended, were not included in the FAS.

China Cohort: The China FAS included all randomized participants in the China cohort and were used for all China only efficacy analyses.

PD-L1 TC ≥25% and PD-L1 TC ≥50% analysis sets included the subset of participants in the FAS whose PD-L1 status was TC ≥25% and TC ≥50% membrane expression in tumoral tissue, respectively at baseline as defined by the Ventana SP263 PD-L1 Assay.

The PFS (per Response Evaluation Criteria in Solid Tumors, version 1.1 \[RECIST 1.1\] using Investigator assessments) was defined as the time from the date of randomization until the date of objective PD or death (by any cause in the absence of progression) regardless of whether the participant withdrew from randomized therapy or received another anticancer therapy prior to progression (ie, date of PFS event or censoring - date of randomization + 1).

bTMB ≥20 mut/Mb, bTMB ≥16 mut/Mb and bTMB ≥12 mut/Mb analysis sets included the subset of participants in FAS whose bTMB status was ≥20 mut/Mb, ≥16 mut/Mb and ≥12 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay.

tTMB ≥14 mut/Mb, tTMB ≥12 mut/Mb, tTMB ≥10 mut/Mb and tTMB ≥8 mut/Mb analysis sets included the subset of participants in FAS whose tTMB status was ≥14 mut/Mb, ≥12 mut/Mb, ≥10 mut/Mb and ≥8 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay.

PFS (per RECIST 1.1 using Investigator assessments) was defined as time from date of randomization until date of objective PD or death regardless of whether participant withdrew from randomized therapy or received another anticancer therapy prior to progression (ie, date of PFS event or censoring - date of randomization + 1).

PD-L1-negative analysis set included subset of participants in FAS whose PD-L1 status was PD-L1-negative at baseline as defined by Ventana SP263 PD-L1 Assay (ie, \<1% PD-L1-membrane expression in tumoral tissue).

Global Cohort: FAS included all randomized participants prior to end of global recruitment.

China Cohort: China FAS included all randomized participants in China cohort and were used for all China only efficacy analyses.

PD-L1 TC ≥25% and PD-L1 TC ≥50% analysis sets included subset of participants in FAS whose PD-L1 status was TC ≥25% and TC ≥50% membrane expression in tumoral tissue, respectively at baseline as defined by the Ventana SP263 PD-L1 Assay.

The ORR (per RECIST 1.1 using Investigator assessments) was defined as the percentage of participants with at least 1 visit response of complete response (CR) or partial response (PR) prior to PD.

bTMB ≥20 mut/Mb, bTMB ≥16 mut/Mb and bTMB ≥12 mut/Mb analysis sets included the subset of participants in FAS whose bTMB status was ≥20 mut/Mb, ≥16 mut/Mb and ≥12 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay.

tTMB ≥14 mut/Mb, tTMB ≥12 mut/Mb, tTMB ≥10 mut/Mb and tTMB ≥8 mut/Mb analysis sets included the subset of participants in FAS whose tTMB status was ≥14 mut/Mb, ≥12 mut/Mb, ≥10 mut/Mb and ≥8 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay.

The ORR (per RECIST 1.1 using Investigator assessments) was defined as the percentage of participants with at least 1 visit response of CR or PR prior to PD.

PD-L1-negative analysis set included the subset of participants in FAS whose PD-L1 status was PD-L1-negative at baseline as defined by the Ventana SP263 PD-L1 Assay (ie, \<1% PD-L1-membrane expression in tumoral tissue).

Global Cohort: The FAS included all randomized participants prior to the end of global recruitment.

China Cohort: The China FAS included all randomized participants in the China cohort and were used for all China only efficacy analyses.

PD-L1 TC ≥25% and PD-L1 TC ≥50% analysis sets included the subset of participants in the FAS whose PD-L1 status was TC ≥25% and TC ≥50% membrane expression in tumoral tissue, respectively at baseline as defined by the Ventana SP263 PD-L1 Assay.

DoR (per RECIST 1.1 using Investigator assessments) was defined as the time from the date of first documented response (CR or PR) until the first date of documented progression or death in the absence of PD (ie, date of PFS event or censoring - date of first response + 1).

bTMB ≥20 mut/Mb, bTMB ≥16 mut/Mb and bTMB ≥12 mut/Mb analysis sets included the subset of participants in FAS whose bTMB status was ≥20 mut/Mb, ≥16 mut/Mb and ≥12 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay.

DoR (per RECIST 1.1 using Investigator assessments) was defined as the time from the date of first documented response (CR or PR) until the first date of documented progression or death in the absence of PD (ie, date of PFS event or censoring - date of first response + 1).

PD-L1-negative analysis set included the subset of participants in FAS whose PD-L1 status was PD-L1-negative at baseline as defined by the Ventana SP263 PD-L1 Assay (ie, \<1% PD-L1-membrane expression in tumoral tissue).

Global Cohort: The FAS included all randomized participants prior to the end of global recruitment.

China Cohort: The China FAS included all randomized participants in the China cohort and were used for all China only efficacy analyses.

The APF12 was defined as the percentage of participants who were alive and progression free at 12 months from randomization (ie, PFS rate at 12 months).

bTMB ≥20 mut/Mb, bTMB ≥16 mut/Mb and bTMB ≥12 mut/Mb analysis sets included the subset of participants in FAS whose bTMB status was ≥20 mut/Mb, ≥16 mut/Mb and ≥12 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay.

The APF12 was defined as the percentage of patients who were alive and progression free at 12 months from randomization (ie, PFS rate at 12 months).

PD-L1-negative analysis set included the subset of participants in FAS whose PD-L1 status was PD-L1-negative at baseline as defined by the Ventana SP263 PD-L1 Assay (ie, \<1% PD-L1-membrane expression in tumoral tissue).

Global Cohort: The FAS included all randomized participants prior to the end of global recruitment.

China Cohort: The China FAS included all randomized participants in the China cohort and were used for all China only efficacy analyses.

The PFS2 was defined as the time from the date of randomization to the earliest of the progression events subsequent to that used for the primary variable PFS, or death (ie, date of PFS2 event or censoring - date of randomization + 1).

bTMB ≥20 mut/Mb, bTMB ≥16 mut/Mb and bTMB ≥12 mut/Mb analysis sets included the subset of participants in FAS whose bTMB status was ≥20 mut/Mb, ≥16 mut/Mb and ≥12 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay.

The PFS2 was defined as the time from the date of randomization to the earliest of the progression events subsequent to that used for the primary variable PFS, or death (ie, date of PFS2 event or censoring - date of randomization + 1).

PD-L1-negative analysis set included the subset of participants in FAS whose PD-L1 status was PD-L1-negative at baseline as defined by the Ventana SP263 PD-L1 Assay (ie, \<1% PD-L1-membrane expression in tumoral tissue).

Global Cohort: The FAS included all randomized participants prior to the end of global recruitment.

China Cohort: The China FAS included all randomized participants in the China cohort and were used for all China only efficacy analyses.

The OS was defined as the time from the date of randomization until death due to any cause (ie, date of death or censoring - date of randomization + 1).

bTMB ≥20 mut/Mb, bTMB ≥16 mut/Mb and bTMB ≥12 mut/Mb analysis sets included the subset of participants in FAS whose bTMB status was ≥20 mut/Mb, ≥16 mut/Mb and ≥12 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay.

The OS was defined as the time from the date of randomization until death due to any cause (ie, date of death or censoring - date of randomization + 1).

PD-L1-negative analysis set included the subset of participants in FAS whose PD-L1 status was PD-L1-negative at baseline as defined by the Ventana SP263 PD-L1 Assay (ie, \<1% PD-L1-membrane expression in tumoral tissue).

Global Cohort: The FAS included all randomized participants prior to the end of global recruitment.

China Cohort: The China FAS included all randomized participants in the China cohort and were used for all China only efficacy analyses.

Blood samples were collected to determine the serum concentration of durvalumab.

Blood samples were collected to determine the serum concentration of tremelimumab.

Blood samples were measured for the presence of ADAs and ADA-neutralizing antibodies (nAb) for durvalumab using validated assays. ADA prevalence is defined as the percentage of participants with positive ADA result at any time, baseline or post-baseline. Treatment-emergent ADA is defined as the sum of treatment-induced ADA and treatment-boosted ADA. ADA incidence is the percentage of participants who were treatment-emergent ADA-positive. Treatment-boosted ADA is defined as baseline positive ADA titer that was boosted to \>=4 fold during the study period. Persistently positive is defined as having at least 2 post baseline ADA positive measurements with at least 16 weeks (112 days) between the first and last positive measurements, or an ADA positive result at the last available assessment. Transiently positive is defined as having at least 1 post baseline ADA positive measurement and not fulfilling the conditions for persistently positive.

Blood samples were measured for the presence of ADAs and ADA-nAb for tremelimumab using validated assays. ADA prevalence is defined as the percentage of participants with positive ADA result at any time, baseline or post-baseline. Treatment-emergent ADA is defined as the sum of treatment-induced ADA and treatment-boosted ADA. ADA incidence is the percentage of participants who were treatment-emergent ADA-positive. Treatment-boosted ADA is defined as baseline positive ADA titer that was boosted to \>=4 fold during the study period. Persistently positive is defined as having at least 2 post baseline ADA positive measurements with at least 16 weeks (112 days) between the first and last positive measurements, or an ADA positive result at the last available assessment. Transiently positive is defined as having at least 1 post baseline ADA positive measurement and not fulfilling the conditions for persistently positive.

AstraZeneca

Global Cohort: The safety analysis set included all participants recruited prior to end of the global recruitment who received at least 1 dose of study treatment.

China Cohort: The China safety analysis set included all participants recruited in the China cohort who received at least 1 dose of study treatment.

All-Cause Mortality: Data from participants included in Global and China FAS was summarized separately. 30 participants in China cohort were also included in Global cohort.

Participants received durvalumab 20 mg/kg and tremelimumab 1 mg/kg IV infusion Q4W in combination for up to 4 doses/cycles. Participants then continued to receive durvalumab 20 mg/kg Q4W, starting on Week 16 until objective PD, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or specific treatment discontinuation criteria were met.

Global: Durvalumab + Tremelimumab

Participants received 1 of the following IV infusion treatment combinations on Day 1 of each 21-day cycle for 4 to 6 cycles or until objective PD, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or specific treatment discontinuation criteria were met.

1. Paclitaxel 200 mg/m\^2 and carboplatin AUC 5 or 6 mg\*min/mL.
2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2. Additional dose of gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous participants only).
3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 mg\*min/mL. Additional dose of gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous participants only).
4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (For non-squamous participants only; pemetrexed maintenance dose was permitted).
5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 mg\*min/mL (For non-squamous participants only; pemetrexed maintenance dose was permitted).

Global: SoC Chemotherapy

China: Durvalumab + Tremelimumab

China: SoC Chemotherapy

All Participants: Durvalumab + Tremelimumab

All Participants: SoC Chemotherapy

Total

All participants

Global cohort

China cohort

Baseline data is presented for all participants, as well as separately for the Global and China cohorts.

Age, Customized

Sex: Female, Male

Race/Ethnicity, Customized

Global Cohort: The full analysis set (FAS) included all randomized participants prior to the end of global recruitment. Any participants recruited in China, after global recruitment had ended, were not included in the FAS.

China Cohort: The China FAS included all randomized participants in the China cohort and were used for all China only efficacy analyses.

Participants included in both cohorts are not double-counted for the baseline characteristics analysis represented by 'All participants'.

Analysis of the China cohort was performed to evaluate the consistency of efficacy and safety in Chinese participants with the global cohort in order to meet China health regulatory requirements and was not powered for a formal assessment of statistical significance.

Global Clinical Lead

Global: Durvalumab + Tremelimumab versus (Vs) Global: SoC Chemotherapy

A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer OS than SoC.

The bTMB ≥20 mut/Mb analysis set included the subset of participants in the FAS whose blood TMB status was ≥20 mut/Mb at baseline as defined by the GuardantOMNI CDx assay. Only participants randomized in Global cohort were analyzed as bTMB and tissue tumor mutational burden (tTMB) testing was not performed in China cohort.

Overall Survival (OS); Global Cohort: Blood Tumor Mutational Burden (bTMB) ≥20 Mutations Per Megabase (Mut/Mb) Analysis Set

China: Durvalumab + Tremelimumab Vs China: SoC Chemotherapy

A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer OS than SoC.

The China PD-L1-negative population analysis set included the subset of participants in the China FAS whose PD-L1 status was PD-L1-negative at baseline as defined by the Ventana SP263 PD-L1 assay (ie, \<1% PD-L1-membrane expression in tumoral tissue). Only participants randomized in China cohort were analyzed.

OS; China Cohort: China Programmed Cell Death Ligand 1 (PD-L1) Negative NSCLC Analysis Set

bTMB ≥16 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy

A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer OS than SoC.

bTMB ≥12 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy

A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer OS than SoC.

PD-L1 negative analysis set:

Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy

A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer OS than SoC.

bTMB \<20 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy

A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer OS than SoC.

bTMB non-evaluable analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy

A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer OS than SoC.

tTMB ≥14 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy

A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer OS than SoC.

tTMB ≥12 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy

A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer OS than SoC.

tTMB ≥10 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy

A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer OS than SoC.

tTMB ≥8 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy

A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer OS than SoC.

bTMB ≥16 mut/Mb analysis set

bTMB ≥12 mut/Mb analysis set

PD-L1 negative analysis set

bTMB <20 mut/Mb analysis set

bTMB non-evaluable analysis set

tTMB ≥14 mut/Mb analysis set

tTMB ≥12 mut/Mb analysis set

tTMB ≥10 mut/Mb analysis set

tTMB ≥8 mut/Mb analysis set

Participants included in bTMB ≥16 mut/Mb, bTMB ≥12 mut/Mb, PD-L1-Negative NSCLC, bTMB \<20 mut/Mb, bTMB non-evaluable population, tTMB ≥14 mut/Mb, tTMB ≥12 mut/Mb, tTMB ≥10 mut/Mb, and tTMB ≥8 mut/Mb analysis sets are reported in this outcome measure. Only participants randomized in Global cohort were analyzed as bTMB and tTMB testing was not performed in China cohort.

OS; Global Cohort: bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, PD-L1-Negative NSCLC, bTMB <20 Mut/Mb, bTMB Non-Evaluable Population, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets

FAS:

Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy

A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer OS than SoC.

FAS:

China: Durvalumab + Tremelimumab Vs China: SoC Chemotherapy

A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer OS than SoC.

PD-L1 TC ≥25% analysis set:

Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy

A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer OS than SoC.

PD-L1 TC ≥ 25% analysis set:

China: Durvalumab + Tremelimumab Vs China: SoC Chemotherapy

A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer OS than SoC.

PD-L1 TC ≥50% analysis set:

Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy

A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer OS than SoC.

PD-L1 TC ≥50% analysis set:

China: Durvalumab + Tremelimumab Vs China: SoC Chemotherapy

A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer OS than SoC.

PD-L1 TC ≥25% analysis set

PD-L1 TC ≥50% analysis set

Participants included in FAS, PD-L1 TC ≥25%, and PD-L1 TC ≥50% analysis sets are reported in this outcome measure.

OS; Global and China Cohorts: FAS, PD-L1 Tumor Cell (TC) ≥25%, and PD-L1 TC ≥50% Analysis Sets

bTMB ≥20 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy

A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer PFS than SoC.

bTMB ≥16 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy

A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer PFS than SoC.

bTMB ≥12 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy

A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer PFS than SoC.

tTMB ≥14 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy

A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer PFS than SoC.

tTMB ≥12 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy

A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer PFS than SoC.

tTMB ≥10 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy

A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer PFS than SoC.

tTMB ≥8 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy

A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer PFS than SoC.

bTMB ≥20 mut/Mb analysis set

Participants included in bTMB ≥20 mut/Mb, bTMB ≥16 mut/Mb, bTMB ≥12 mut/Mb, tTMB ≥14 mut/Mb, tTMB ≥12 mut/Mb, tTMB ≥10 mut/Mb, and tTMB ≥8 mut/Mb analysis sets are reported in this outcome measure. Only participants randomized in Global cohort were analyzed as bTMB and tTMB testing was not performed in China cohort.

Progression-Free Survival (PFS); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets

PD-L1-negative analysis set:

Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy

A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer PFS than SoC.

PD-L1-negative analysis set:

China: Durvalumab + Tremelimumab Vs China: SoC Chemotherapy

A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer PFS than SoC.

FAS:

Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy

A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer PFS than SoC.

FAS:

China: Durvalumab + Tremelimumab Vs China: SoC Chemotherapy

A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer PFS than SoC.

PD-L1 TC ≥25% analysis set:

Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy

A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer PFS than SoC.

PD-L1 TC ≥ 25% analysis set:

China: Durvalumab + Tremelimumab Vs China: SoC Chemotherapy

A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer PFS than SoC.

PD-L1 TC ≥50% analysis set:

Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy

A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer PFS than SoC.

PD-L1 TC ≥50% analysis set:

China: Durvalumab + Tremelimumab Vs China: SoC Chemotherapy

A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer PFS than SoC.

PD-L1-negative NSCLC analysis set

Participants included in PD-L1-negative NSCLC, FAS, PD-L1 TC ≥25%, and PD-L1 TC ≥50% analysis sets are reported in this outcome measure.

PFS; Global and China Cohorts: PD-L1-Negative NSCLC, FAS, PD-L1 TC ≥25%, and PD-L1 TC ≥50% Analysis Sets

bTMB ≥20 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy

An odds ratio \>1 favors Durvalumab + Tremelimumab combination therapy over SoC.

bTMB ≥16 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy

An odds ratio \>1 favors Durvalumab + Tremelimumab combination therapy over SoC.

bTMB ≥12 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy

An odds ratio \>1 favors Durvalumab + Tremelimumab combination therapy over SoC.

tTMB ≥14 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy

An odds ratio \>1 favors Durvalumab + Tremelimumab combination therapy over SoC.

tTMB ≥12 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy

An odds ratio \>1 favors Durvalumab + Tremelimumab combination therapy over SoC.

tTMB ≥10 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy

An odds ratio \>1 favors Durvalumab + Tremelimumab combination therapy over SoC.

tTMB ≥8 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy

An odds ratio \>1 favors Durvalumab + Tremelimumab combination therapy over SoC.

Participants included in bTMB ≥20 mut/Mb, bTMB ≥16 mut/Mb, bTMB ≥12 mut/Mb, tTMB ≥14 mut/Mb, tTMB ≥12 mut/Mb, tTMB ≥10 mut/Mb, and tTMB ≥8 mut/Mb analysis sets with measurable disease are reported in this outcome measure. Only participants randomized in Global cohort were analyzed as bTMB and tTMB testing was not performed in China cohort.

Objective Response Rate (ORR); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets

PD-L1-negative analysis set:

Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy

An odds ratio \>1 favors Durvalumab + Tremelimumab combination therapy over SoC.

PD-L1-negative analysis set:

China: Durvalumab + Tremelimumab Vs China: SoC Chemotherapy

An odds ratio \>1 favors Durvalumab + Tremelimumab combination therapy over SoC.

FAS:

Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy

An odds ratio \>1 favors Durvalumab + Tremelimumab combination therapy over SoC.

FAS:

China: Durvalumab + Tremelimumab Vs China: SoC Chemotherapy

An odds ratio \>1 favors Durvalumab + Tremelimumab combination therapy over SoC.

PD-L1 TC ≥25% analysis set:

Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy

An odds ratio \>1 favors Durvalumab + Tremelimumab combination therapy over SoC.

PD-L1 TC ≥ 25% analysis set:

China: Durvalumab + Tremelimumab Vs China: SoC Chemotherapy

An odds ratio \>1 favors Durvalumab + Tremelimumab combination therapy over SoC.

PD-L1 TC ≥50% analysis set:

Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy

An odds ratio \>1 favors Durvalumab + Tremelimumab combination therapy over SoC.

PD-L1 TC ≥50% analysis set:

China: Durvalumab + Tremelimumab Vs China: SoC Chemotherapy

An odds ratio \>1 favors Durvalumab + Tremelimumab combination therapy over SoC.

Participants included in PD-L1-negative NSCLC, FAS, PD-L1 TC ≥25%, and PD-L1 TC ≥50% analysis sets with measurable disease are reported in this outcome measure.

ORR; Global and China Cohorts: PD-L1-Negative NSCLC, FAS, PD-L1 TC ≥25%, and PD-L1 TC ≥50% Analysis Sets

bTMB ≥20 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy

A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer DoR than SoC.

bTMB ≥16 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy

A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer DoR than SoC.

bTMB ≥12 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy

A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer DoR than SoC.

Participants included in bTMB ≥20 mut/Mb, bTMB ≥16 mut/Mb, and bTMB ≥12 mut/Mb analysis sets are reported in this outcome measure. Only participants with objective response and randomized in Global cohort were analyzed as bTMB and tTMB testing was not performed in China cohort.

Duration of Response (DoR); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets

PD-L1-negative analysis set:

Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy

A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer DoR than SoC.

PD-L1-negative analysis set:

China: Durvalumab + Tremelimumab Vs China: SoC Chemotherapy

A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer DoR than SoC.

FAS:

Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy

A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer DoR than SoC.

FAS:

China: Durvalumab + Tremelimumab Vs China: SoC Chemotherapy

A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer DoR than SoC.

Participants included in PD-L1-negative NSCLC and FAS analysis sets are reported in this outcome measure. Only participants with objective response were included in this analysis.

DoR; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets

Participants included in bTMB ≥20 mut/Mb, bTMB ≥16 mut/Mb, and bTMB ≥12 mut/Mb analysis sets are reported in this outcome measure. Only participants randomized in Global cohort were analyzed as bTMB and tTMB testing was not performed in China cohort.

Alive and Progression-Free at 12 Months (APF12); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets

Participants included in PD-L1-negative NSCLC and FAS analysis sets are reported in this outcome measure.

APF12; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets

bTMB ≥20 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy

A HR \<1 favors Durvalumab + Tremelimumab to be associated with a longer time to second progression than SoC.

bTMB ≥16 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy

A HR \<1 favors Durvalumab + Tremelimumab to be associated with a longer time to second progression than SoC.

bTMB ≥12 mut/Mb analysis set: Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy

A HR \<1 favors Durvalumab + Tremelimumab to be associated with a longer time to second progression than SoC.

Time From Randomization to Second Progression or Death (PFS2); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets

PD-L1-negative analysis set:

Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy

A HR \<1 favors Durvalumab + Tremelimumab to be associated with a longer time to second progression than SoC.

PD-L1-negative analysis set:

China: Durvalumab + Tremelimumab Vs China: SoC Chemotherapy

A HR \<1 favors Durvalumab + Tremelimumab to be associated with a longer time to second progression than SoC.

FAS:

Global: Durvalumab + Tremelimumab Vs Global: SoC Chemotherapy

A HR \<1 favors Durvalumab + Tremelimumab to be associated with a longer time to second progression than SoC.

FAS:

China: Durvalumab + Tremelimumab Vs China: SoC Chemotherapy

A HR \<1 favors Durvalumab + Tremelimumab to be associated with a longer time to second progression than SoC.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Study of Durvalumab With Tremelimumab Versus SoC as 1st Line Therapy in Metastatic Non Small-Cell Lung Cancer (NSCLC) (NEPTUNE)	NCT02542293	Non Small Cell ...	Durvalumab +Tre... Paclitaxel + ca... Gemcitabine + c... Gemcitabine + c... Pemetrexed + ci... Pemetrexed + ca...	18 Years - 130 Years	AstraZeneca
Study of Durvalumab With Tremelimumab Versus SoC as 1st Line Therapy in Metastatic Non Small-Cell Lung Cancer (NSCLC) (NEPTUNE)	NCT02542293	Non Small Cell ...	Durvalumab +Tre... Paclitaxel + ca... Gemcitabine + c... Gemcitabine + c... Pemetrexed + ci... Pemetrexed + ca...	18 Years - 130 Years	AstraZeneca

Spots Global Cancer Trial Database for durvalumab +tremelimumab